Natural Product: NPC248490

Natural Product IDNPC248490
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VSUOKLTVXQRUSG-UNJWAJPSSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 25202164
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0002934] Flavonoid O-glucuronides
              • [CHEMONTID:0003534] Flavonoid-7-O-glucuronides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey VSUOKLTVXQRUSG-UNJWAJPSSA-N
Standard InCHI InChI=1S/C21H18O12/c22-9-2-1-7(3-10(9)23)13-6-12(25)15-11(24)4-8(5-14(15)32-13)31-21-18(28)16(26)17(27)19(33-21)20(29)30/h1-6,16-19,21-24,26-28H,(H,29,30)/t16-,17-,18+,19-,21-/m0/s1
SMILES c1cc(c(cc1c1cc(=O)c2c(cc(cc2o1)O[C@@H]1[C@@H]([C@H]([C@@H]([C@@H](C(=O)O)O1)O)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.08 Volume:   419.301
?
Van der Waals volume.
Dense:   1.102 LogP:   0.954
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.259
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.156
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   25.0
TPSA:   207.35
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   7.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.253 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.992 Fsp3:   0.238
MCE-18:   91.385
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.49 Fluc inhibitor:   0.334
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.982
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.879
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.311 Promiscuous compounds:   0.476

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.492 MDCK Permeability:   -5.116
Pgp-inhibitor:   0.0 Pgp-substrate:   0.495
PAMPA:   1.0
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.875
20% Bioavailability (F20%):   0.974 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.97
Plasma Protein Binding (PPB):   81.406% Volume Distribution (VD):   -0.024
Fu: 14.836%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.053
OATP1B3 inhibitor:   0.557 BCRP inhibitor:   0.093
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.031
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.443
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.957
HLM stability:   0.014
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  1.725 Half-life (T1/2):  3.294

ADMET: Toxicity

hERG Blockers:  0.006 hERG Blockers (10um):  0.081
Human Hepatotoxicity (H-HT):  0.488 Drug-induced Liver Injury (DILI):  0.991
AMES Toxicity:  0.86 Rat Oral Acute Toxicity:  0.12
Maximum Recommended Daily Dose:  0.154 Skin Sensitization:  0.999
Carcinogencity:  0.083 Eye Corrosion:  0.0
Eye Irritation:  0.863 Respiratory Toxicity:  0.091
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.675
Hematotoxicity:  0.101 Drug-induced Nephrotoxicity:  0.464
Genotoxicity:  0.977 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.674 Hek293 Cytotoxicity:  0.212
BCF:   0.263
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   2.858
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.269
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.445
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96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO16108 Eupatorium mikanioides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16108 Eupatorium mikanioides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15042 Lepraria membranacea Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16108 Eupatorium mikanioides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC248490 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC20505
0.8889 High Similarity NPC282169
0.8267 Intermediate Similarity NPC608742
0.7273 Intermediate Similarity NPC253685
0.7215 Intermediate Similarity NPC135277
0.6923 Remote Similarity NPC19709
0.6914 Remote Similarity NPC43211
0.6835 Remote Similarity NPC189142
0.6835 Remote Similarity NPC77660
0.6818 Remote Similarity NPC229409
0.6667 Remote Similarity NPC600989
0.6585 Remote Similarity NPC237435
0.6386 Remote Similarity NPC210094
0.6353 Remote Similarity NPC190003
0.631 Remote Similarity NPC115760
0.6207 Remote Similarity NPC606546
0.6197 Remote Similarity NPC108406
0.619 Remote Similarity NPC235260
0.619 Remote Similarity NPC155763
0.6118 Remote Similarity NPC610187
0.6071 Remote Similarity NPC101191
0.6044 Remote Similarity NPC64051
0.6 Remote Similarity NPC49344
0.6 Remote Similarity NPC210073
0.5976 Remote Similarity NPC473043
0.5976 Remote Similarity NPC331652
0.5904 Remote Similarity NPC39360
0.5904 Remote Similarity NPC29763
0.5904 Remote Similarity NPC210003
0.5843 Remote Similarity NPC8856
0.5806 Remote Similarity NPC65711
0.5789 Remote Similarity NPC605587
0.5747 Remote Similarity NPC601144
0.5699 Remote Similarity NPC46202
0.5698 Remote Similarity NPC27942
0.5591 Remote Similarity NPC115674
0.5568 Remote Similarity NPC22832
0.5529 Remote Similarity NPC261866
0.5517 Remote Similarity NPC138927
0.5506 Remote Similarity NPC311830
0.5495 Remote Similarity NPC107987
0.5465 Remote Similarity NPC95090
0.5465 Remote Similarity NPC27408
0.5402 Remote Similarity NPC181712
0.5349 Remote Similarity NPC238376
0.5287 Remote Similarity NPC277205
0.5287 Remote Similarity NPC37919
0.5287 Remote Similarity NPC136042
0.5227 Remote Similarity NPC58716
0.5227 Remote Similarity NPC84362
0.5227 Remote Similarity NPC45638
0.5222 Remote Similarity NPC243930
0.5213 Remote Similarity NPC44931
0.52 Remote Similarity NPC234133
0.52 Remote Similarity NPC484301
0.5169 Remote Similarity NPC201292
0.5114 Remote Similarity NPC168822
0.5056 Remote Similarity NPC271692
0.5055 Remote Similarity NPC264735
0.5051 Remote Similarity NPC270675
0.5051 Remote Similarity NPC195685

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC248490 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6585 Remote Similarity NPD4338 Clinical (unspecified phase)

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data